Objectives: An association is found between changes in cytokine levels and antidepressant treatment outcome. Also, a proinflammatory profile is associated with a favourable electroconvulsive therapy (ECT) outcome. This paper investigates the pattern of inflammatory markers during a course of ECT in older depressed patients and whether this pattern is associated with ECT outcome. We hypothesised that ECT has an anti-inflammatory effect. Methods: The pattern of CRP, IL-6, IL-10, and TNF-α during a course of ECT was examined using longitudinal mixed model analyses. Serum samples were collected in 99 older depressed patients (mean age: 72.8 ± 8.3 years, MADRS score 33.8 ± 9.0). Results: After Bonferroni correction, there were no statistically significant alterations in levels of inflammatory markers during and after ECT. Effect sizes (Cohen’s d) were −0.29 for CRP, −0.13 for IL-6, −0.06 for IL-10, and −0.07 for TNF-α. Changes in CRP or cytokine levels did not differ between remitters and non-remitters. Median baseline levels of CRP were significantly higher in remitters. Conclusions: A small to medium effect size towards decreased CRP and IL-6 levels was observed. An anti-inflammatory effect of ECT could not be confirmed. However, the findings may suggest that patients with an inflammatory profile benefit more from ECT than other patients. Further studies are needed to confirm these findings.